Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM03SFL)

• DOT Name: GPN-loop GTPase 1 (GPN1)
• Synonyms: EC 3.6.5.-; MBD2-interacting protein; MBDin; RNAPII-associated protein 4; XPA-binding protein 1
• Gene Name: GPN1
• Related Disease:
  Advanced cancer
  Gout
  Oral cancer
• UniProt ID: GPN1_HUMAN
• EC Number: 3.6.5.-
• Pfam ID: PF03029
• Sequence:
  MAASAAAAELQASGGPRHPVCLLVLGMAGSGKTTFVQRLTGHLHAQGTPPYVINLDPAVH
  EVPFPANIDIRDTVKYKEVMKQYGLGPNGGIVTSLNLFATRFDQVMKFIEKAQNMSKYVL
  IDTPGQIEVFTWSASGTIITEALASSFPTVVIYVMDTSRSTNPVTFMSNMLYACSILYKT
  KLPFIVVMNKTDIIDHSFAVEWMQDFEAFQDALNQETTYVSNLTRSMSLVLDEFYSSLRV
  VGVSAVLGTGLDELFVQVTSAAEEYEREYRPEYERLKKSLANAESQQQREQLERLRKDMG
  SVALDAGTAKDSLSPVLHPSDLILTRGTLDEEDEEADSDTDDIDHRVTEESHEEPAFQNF
  MQESMAQYWKRNNK
• Function: Small GTPase required for proper nuclear import of RNA polymerase II (RNAPII). May act at an RNAP assembly step prior to nuclear import. Forms an interface between the RNA polymerase II enzyme and chaperone/scaffolding proteins, suggesting that it is required to connect RNA polymerase II to regulators of protein complex formation. May be involved in nuclear localization of XPA.
• Tissue Specificity: Expressed ubiquitously.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Genetic Variation	[1]
Gout	DISHC0U7	Strong	Genetic Variation	[2]
Oral cancer	DISLD42D	Strong	Genetic Variation	[3]

11 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of GPN-loop GTPase 1 (GPN1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of GPN-loop GTPase 1 (GPN1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of GPN-loop GTPase 1 (GPN1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of GPN-loop GTPase 1 (GPN1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of GPN-loop GTPase 1 (GPN1).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of GPN-loop GTPase 1 (GPN1).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of GPN-loop GTPase 1 (GPN1).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of GPN-loop GTPase 1 (GPN1).	[11]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the expression of GPN-loop GTPase 1 (GPN1).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of GPN-loop GTPase 1 (GPN1).	[12]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of GPN-loop GTPase 1 (GPN1).	[13]

References

• [1] The Gpn3 Q279* cancer-associated mutant inhibits Gpn1 nuclear export and is deficient in RNA polymerase II nuclear targeting.FEBS Lett. 2017 Nov;591(21):3555-3566. doi: 10.1002/1873-3468.12856. Epub 2017 Oct 11.
• [2] Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet. 2013 Feb;45(2):145-54. doi: 10.1038/ng.2500. Epub 2012 Dec 23.
• [3] Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer.Nat Genet. 2016 Dec;48(12):1544-1550. doi: 10.1038/ng.3685. Epub 2016 Oct 17.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] Synergistic effects of arsenic trioxide combined with ascorbic acid in human osteosarcoma MG-63 cells: a systems biology analysis. Eur Rev Med Pharmacol Sci. 2014;18(24):3877-88.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.